Why "muscle-sparing" is a marketing term and not a measurement
The gap between a defensible recommendation and a confident one is where most of the harm in this subject lives.
Tirzepatide
Page 17 of 18 of this archive, newest first.
SURPASS-3 was built to answer the stopping question, and it did
What was withdrawn, from whom, after how long, and what was measured afterwards.
The imaging substudy is an afterthought in the protocol and the centrepiece of the debate
The composition data comes from imaging substudies enrolling a few score participants at selected sites. It is the best evidence available and it is thin.
From 0.25 to 2.4: reading a ladder as a series of ratios
What the published pharmacokinetics permit, what the labels state, and where the two diverge.
The glucagon receptor arm, and why it is the hardest to reason about
Head-to-head data exists for some of these comparisons and not for others. This piece says which.
The label says four weeks. The clinic says whatever holds.
What the regulatory dossiers actually contain on dose selection is remarkably thin, and worth knowing before treating the ladder as settled science.
Why the bone question is harder than the muscle question
The evidence base is one secondary analysis, several small studies and a large amount of extrapolation from bariatric surgery.
Two sessions a week, and the evidence behind the prescription
Mass and function are different endpoints and training affects them differently. Most coverage treats them as one.
The trade has decided the ceiling is arbitrary. The trials disagree.
The ceiling in this class is anatomical: the same receptor populations that suppress appetite provoke nausea, and they saturate together.
The ceiling is a tolerability finding, not an efficacy one
Where the curve flattens, what flattens with it, and what does not.
The shortage years, and what they taught about interruption
A supply interruption is a discontinuation with no notice, no taper and no plan. That is a distinct clinical situation.
Which results should be repeated before they are investigated
What the pivotal programmes measured and how often, which is a more defensible template than most published monitoring schedules.
What the cagrilintide schedule assumes about a person it has never met
The four-week step exists because four to five weeks is approximately how long a once-weekly drug takes to stop rising at a fixed dose. That is a good reason, and it is not…
Escalating past the approved maximum, examined honestly
Where the curve flattens, what flattens with it, and what does not.
The arithmetic of a step: what doubling a dose actually asks of you
What the published pharmacokinetics permit, what the labels state, and where the two diverge.
What happens when the drug is taken away: three randomised answers
Three randomised withdrawal designs have tested what happens when treatment stops. Their results are consistent and they are consistently misreported.
Why the bone question is harder than the muscle question
Weight loss reduces bone mineral density at load-bearing sites. Whether that translates into fractures in this population is unmeasured.
Why receptor selectivity is the least discussed number in incretin pharmacology
Selectivity, potency and efficacy are three different measurements. The trade routinely reports none of them.
Seasonal use, holiday use, and the honest state of the evidence
A great deal of practice has grown up around intermittent schedules. The randomised evidence for any of them is, as far as the Journal can establish, nil.
Albumin, fatty-acid chains, and the engineering that made a weekly incretin possible
The molecular engineering that turned a peptide with a two-minute half-life into a once-weekly drug.